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Updated: Aug 30, 2025
In Silico Identification and Characterization of circRNAs During Host-Pathogen Interactions
Published on: October 21, 2022
Bioinformatics analysis of the circRNA-miRNA-mRNA network for atrial fibrillation
Xing Liu1, Yiqian Zeng2, Zhao Liu2
1Department of Cardiology, Xiangtan Central Hospital, Xiangtan, Hunan, China.
Insights
Circular RNAs (circRNAs) play a role in atrial fibrillation (AF) pathogenesis. This study identifies key circRNA-miRNA-mRNA regulatory axes, including specific circRNAs and hub genes like CXCR4, potentially involved in AF development.
Area of Science:
- Molecular Biology
- Genetics
- Cardiovascular Research
Background:
- Atrial fibrillation (AF) is a progressive condition with increasing morbidity in aging populations.
- Circular RNAs (circRNAs) are emerging as significant factors in AF development.
- Understanding the regulatory mechanisms involving circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) is crucial for AF research.
Purpose of the Study:
- To explore the regulatory mechanism of circRNAs in atrial fibrillation (AF).
- To investigate the intricate interactions among circRNAs, miRNAs, and mRNAs in AF.
- To construct a competing endogenous RNA (ceRNA) network and identify key regulatory axes.
Main Methods:
- Differential expression analysis of circRNAs, miRNAs, and mRNAs from Gene Expression Omnibus datasets (GSE129409, GSE68475, GSE79768) in AF.
- Construction of a ceRNA network based on circRNA-miRNA and miRNA-mRNA interactions.
- Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and protein-protein interaction (PPI) network construction to identify hub genes.
Main Results:
- Screened 103 differentially expressed (DE) circRNAs, 16 DE miRNAs, and 110 DE mRNAs in AF.
- Constructed a ceRNA network involving specific upregulated and downregulated circRNAs, miRNAs, and mRNAs.
- Identified 6 hub genes (including CXCR4, CXCR2, CXCL11) and a circRNA-miRNA-hub gene subnetwork with 10 regulatory axes.
Conclusions:
- Specific circRNA-miRNA-hub gene regulatory axes, such as hsa_circRNA_0056281/hsa_circRNA_0006665 -hsa-miR-613-CXCR4/CXCR2/CXCL11 and hsa_circRNA_0003638-hsa-miR-1207-3p-CXCR4, are implicated in the pathogenesis of AF.
- These findings provide novel insights into the molecular mechanisms underlying AF and potential therapeutic targets.
Abstract:
Atrial fibrillation (AF) is a chronic and progressive disease, with advancing age, the morbidity of which will increase exponentially. Circular ribonucleic acids (RNAs; circRNAs) have gained a growing attention in the development of AF in recent years. The purpose of this study is to explore the mechanism of circRNA regulation in AF, in particular, the intricate interactions among circRNA, microRNA (miRNA), and messenger RNA (mRNA). Three datasets (GSE129409, GSE68475, and GSE79768) were obtained from the Gene Expression Omnibus database to screen differentially expressed (DE) circRNAs, DE miRNAs, and DE mRNAs in AF, respectively. Based on circRNA-miRNA pairs and miRNA-mRNA pairs, a competing endogenous RNAs (ceRNAs) network was built. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of DE mRNAs in the network were performed and protein-protein interaction (PPI) networks were established to identify hub genes. Finally, a circRNA-miRNA-hub gene subnetwork was constructed. A total of 103 DE circRNAs, 16 DE miRNAs, and 110 DE mRNAs were screened in AF. Next, ceRNAs network in AF was constructed with 3 upregulated circRNAs, 2 downregulated circRNAs, 2 upregulated miRNAs, 2 downregulated miRNAs, 17 upregulated mRNAs, and 24 downregulated mRNAs. Thirty GO terms and 6 KEGG pathways were obtained. Besides, 6 hub genes (C-X-C chemokine receptor type 4 [CXCR4], C-X-C chemokine receptor type 2 [CXCR2], C-X-C motif chemokine 11 [CXCL11], neuromedin-U, B1 bradykinin receptor, and complement C3) were screened from constructing a PPI network. Finally, a circRNA-miRNA-hub gene subnetwork with 10 regulatory axes was constructed to describe the interactions among the differential circRNAs, miRNA, and hub genes. We speculated that hsa_circRNA_0056281/hsa_circRNA_0006665 -hsa-miR-613-CXCR4/CXCR2/CXCL11 regulatory axes and hsa_circRNA_0003638-hsa-miR-1207-3p-CXCR4 regulatory axis may be associated with the pathogenesis of AF.
